The major focus of the Cancer Cell Networks Program is to promote invesfigafion that will contribute to the generafion of a mechanisfic understanding of aberrant cell regulatory networks supporting tumorigenesis. Our faculty approach this problem from multiple levels of mechanistic resolution, spanning atomic structure through animal models. To promote cancer relevance and synergy across Cancer Center efforts our scientific goals are to: (1) Define the mechanisms and pathways that integrate external and internal regulatory cues at the cell autonomous level: This is a traditional strength at UT Southwestern that is leveraged in the Cancer Cell Networks program to define the basal regulatory states that generate and maintain appropriate restraints on cell growth, proliferation and survival. This goal is integrated with the Molecular Therapeutics and Development and Cancer programs in order to capitalize on the leading-edge human cell model systems and vertebrate genetics being developed in those programs. (2) Establish how aberrant cell regulatory behavior contributes to cell transformation and tumorigenesis: Novel experimental strategies and emerging technology platforms are being employed to isolate the condifional molecular dependencies in tumorigenic regulatory environments that represent authenfic diagnostic or therapeutic targets. This goal is heavily integrated with the Molecular Therapeufics of Cancer Scientific Program to promote study designs that maintain translational relevance through incorporafion of appropriate pafient samples and disease data. Importanfiy, integrafion of this goal with the Chemistry and Cancer program is facilitafing the generation of small molecule leads for in vitro and in vivo target validation and development. (3) Facilitate interactions with translational and clinical scientists to develop strategies to test the therapeutic benefit of modulating cell regulatory components: The Cancer Center leadership has fostered an atmosphere of communication and collaboration between basic science investigators, with expertise in mechanisfic relafionships governing cell behavior, and clinical researchers with acute knowledge and appreciation of the human disease. This both elevates the ability of basic scienfists to develop experimental strategies with greater cancer relevance, and empowers clinicians to move beyond cataloging of cancerassociated phenomena toward defining mechanisfic properties at molecular resolufion.